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Global Translational Medicine Small RNA therapy for pancreatic cancer

(DMD), and familial amyloidotic polyneuropathy Ruibo Biotech has developed its proprietary RIBO-
(Table 4). GalSTAR delivery technology, which significantly enhances
The development of these small RNA drugs is the liver-targeting efficiency of siRNA. The company’s
predominantly led by six companies, including Alnylam research efforts focus on metabolic diseases, cardiovascular
(https://www.alnylam.com), Ionis (https://www. diseases, and liver disorders. While Ruibo Biotech has yet
ionispharma.com), Sarepta (https://www.sarepta.com), to bring a drug to market, its rapidly advancing pipeline
Arrowhead (https://www.arrowheadpharma.com), demonstrates substantial potential for future growth and
Sirnaomics (https://www.sirnaomics.com), and Ruibo development.
(https://www.ribobio.com). As of January 2025, in addition to the 17 approved drugs,
Alnylam, a pioneer in the field of RNAi, has successfully 44 small RNA drug candidates are in clinical trials. Details
commercialized multiple drugs, including patisiran, givosiran, of these drug candidates are shown in Table 5. These include
lumasiran, and inclisiran. The company has developed a 25 siRNA drugs, 10 ASO drugs, six miRNA mimics, and
proprietary N-acetylgalactosamine (GalNAc) delivery system three miRNA inhibitors. These small RNA drug candidates
that efficiently delivers siRNA to liver tissue. At present, cover a wide range of diseases, including genetic disorders
Alnylam’s research pipeline covers multiple therapeutic areas, (such as primary hyperoxaluria types 1 and 2, hemophilia A
including rare diseases, metabolic diseases, cardiovascular and B, and familial hypercholesterolemia), cardiovascular
diseases, and central nervous system disorders. diseases (hypertension, atherosclerosis, and heart failure),
liver diseases (hepatitis B, non-alcoholic steatohepatitis,
Ionis is a leader in ASO therapeutics and has and hepatocellular carcinoma), ocular diseases (dry eye
successfully commercialized multiple drugs, including disease with Sjögren syndrome, elevated intraocular
nusinersen, inotersen, volanesorsen, and eplontersen. The pressure, diabetic macular edema, and wet age-related
company has developed proprietary chemical modification macular degeneration), cancers (PC, solid tumor cancers,
technologies that enhance the stability, targeting, and and hematologic malignancies), and kidney diseases (acute
therapeutic efficacy of ASOs. At present, Ionis’ research kidney injury), among others.
pipeline covers multiple therapeutic areas, including rare
diseases, metabolic diseases, cardiovascular diseases, and In summary, small RNA drugs are highly active in
neurological disorders. clinical trials and cover a wide range of disease areas,
demonstrating their immense potential. With continuous
Similarly, Sarepta is a leader in the treatment of DMD,
with three marketed ASO drugs, including eteplirsen, advancements in delivery systems, siRNA drugs currently
lead the field, whereas ASO and miRNA technologies
golodirsen, and casimersen. In addition to DMD, Sarepta’s are also advancing rapidly. Interestingly, no miRNA-
research pipeline focuses on other rare diseases, including
Limb-Girdle muscular dystrophy. based drugs have reached the market, and many have
been discontinued during clinical trials. This may be due
Arrowhead focuses on the development and to the inherent complexity of miRNAs, which typically
commercialization of RNAi-based technologies, with target multiple sites, making it challenging to precisely
currently marketed drugs including vutrisiran and define their mechanisms of action. As a result, ensuring
givosiran. The company has developed proprietary targeted patient safety remains a significant challenge in the clinical
™
delivery platforms, including TRiM (Targeted RNAi development of miRNA therapeutics.
Molecule) and Dynamic Polyconjugate technologies, which
enhance the stability, targeting, and therapeutic efficacy 4.3. Advantages and challenges of small RNA drugs
of siRNA. Arrowhead’s research pipeline spans multiple RNA-based therapies offer three key advantages. First,
therapeutic areas, including rare diseases, metabolic small RNA drugs can target both protein-coding and
disorders, cardiovascular diseases, and liver diseases. non-coding genes, enabling precise regulation of gene
Sirnaomics has developed a proprietary peptide expression, thus offering broad therapeutic potential.
nanoparticle delivery platform to enhance the stability, Second, the design and synthesis of small RNA drugs are
targeting, and therapeutic efficacy of siRNA. The company rapid, allowing them to quickly advance into pre-clinical
focuses on common diseases, including cancer, fibrotic and clinical studies. The accumulated knowledge from
diseases, and metabolic disorders. In addition, they utilize prior research in RNA characterization continues to
a unique dual-targeting delivery technology to enhance expedite this process. Third, small RNA drugs can exert
treatment efficacy. Although Sirnaomics currently has no sustained effects on cells, potentially achieving long-term
marketed drugs, its research direction and technology hold therapeutic outcomes with a single dose. For instance,
significant potential for future development. recent clinical trials have demonstrated that siRNAs drugs

Volume 4 Issue 2 (2025) 21 doi: 10.36922/gtm.8247